Off Label Uses

Stress ulcer prophylaxis in critically-ill patients

Data from a prospective randomized clinical trial in patients at high risk for stress ulcer prophylaxis administered either omeprazole or IV ranitidine, support the use of omeprazole for the prevention of stress ulcers [Levy 1997]. Additional trials may be necessary to further define the role of omeprazole in this setting.

OTC labeling: When used for self-medication (OTC), do not use if trouble or pain when swallowing food; vomiting with blood, or bloody or black stools; heartburn with lightheadedness, dizziness, or sweating; chest pain or shoulder pain with shortness of breath, sweating, pain spreading to arms, neck or shoulders, or lightheadedness; frequent chest pain.

Dosing: Adult

Duodenal ulcer: Oral: 20 mg once daily for 4 weeks; some patients may require an additional 4 weeks. Up to 40 mg once daily has been used in patients with ulcers refractive to other therapies (eg, H2 antagonists) (Bardhan 1991).

Gastric ulcers: Oral: 40 mg once daily for 4 to 8 weeks; in clinical trials, healing rates of ulcers ≤1 cm at 4 and 8 weeks were similar between omeprazole 20 mg and 40 mg; for ulcers >1 cm omeprazole 40 mg was significantly more effective at 8 weeks.

Erosive esophagitis: Oral:

Treatment:

Manufacturer's labeling: 20 mg once daily for 4 to 8 weeks; may continue for an additional 4 weeks if no response to 8 weeks of treatment. With recurrence of erosive esophagitis or GERD symptoms (eg, heartburn), an additional 4 to 8 weeks of treatment may be considered.

Dual therapy: 40 mg once daily administered with clarithromycin 500 mg 3 times daily for 14 days. In patients with presence of ulcer at time of therapy initiation, continue omeprazole 20 mg once daily for an additional 14 days after completion of dual therapy.

Triple therapy: 20 mg twice daily administered with amoxicillin 1,000 mg and clarithromycin 500 mg twice daily for 10 days. In patients with presence of ulcer at time of therapy initiation, continue omeprazole 20 mg once daily for an additional 18 days after completion of triple therapy.

American College of Gastroenterology guidelines (Chey 2007; Chey 2017):

Pathological hypersecretory conditions: Oral: Initial: 60 mg once daily; doses up to 120 mg 3 times daily have been administered; administer daily doses >80 mg in divided doses. Treat as long as clinically indicated; some patients have been treated continuously for >5 years.

Heartburn (OTC only): Oral: 20 mg once daily for 14 days; treatment may be repeated after 4 months if needed.

Dosing: Geriatric

Refer to adult dosing. Bioavailability may be increased in elderly patients.

Dosing: Pediatric

Symptomatic GERD: Children ≥1 year to Adolescents ≤16 years: Oral:

5 kg to <10 kg: 5 mg once daily for up to 4 weeks

10 kg to <20 kg: 10 mg once daily for up to 4 weeks

≥20 kg: 20 mg once daily for up to 4 weeks

Erosive esophagitis, treatment:

Infants 1 month to <1 year: Oral:

3 kg to <5 kg: 2.5 mg once daily for up to 6 weeks

5 kg to <10 kg: 5 mg once daily for up to 6 weeks

≥10 kg: 10 mg once daily for up to 6 weeks

Children ≥1 year to Adolescents ≤16 years: Oral: Note: Duration of therapy is up to 4 to 8 weeks; may continue for an additional 4 weeks if no response to 8 weeks of treatment. With recurrence of erosive esophagitis or GERD symptoms (eg, heartburn), an additional 4 to 8 week course may be considered.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

Mild to severe impairment (Child-Pugh class A, B, or C): 10 mg once daily when used for maintenance of healing of erosive esophagitis. There are no dosage adjustments provided for the other indications. Alternatively, a maximum dose of 20 mg/day regardless of indication, has been recommended (Losec Canadian product labeling). In a very small study, omeprazole systemic exposure and half-life increased ~2- and ~3-fold respectively, in patients with mild to severe hepatic impairment.

Reconstitution

Granules for oral suspension: For oral administration, empty the contents of the 2.5 mg packet into 5 mL of water (10 mg packet into 15 mL of water); stir. For NG administration, add 5 mL of water into a catheter-tipped syringe, and then add the contents of a 2.5 mg packet (15 mL water for the 10 mg packet); immediately shake syringe. Note: Regardless of the route of administration, the suspension should be left to thicken for 2 to 3 minutes prior to administration.

Administration

Administer 30 to 60 minutes before meals; may take with antacids. If administering twice daily, first dose should be administered before breakfast and the second dose before dinner (ACG [Katz 2013]; Herschovici 2010).

Oral:

Capsule: Swallow whole; do not chew or crush. Capsule may be opened and contents mixed with 1 tablespoon of applesauce (soft enough to swallow without chewing). Swallow immediately with a glass of cool water; mixture should not be chewed, crushed, warmed, or saved for future use.

Oral suspension: Following reconstitution, the suspension should be left to thicken for 2 to 3 minutes and administered within 30 minutes. If any material remains after administration, add more water, stir, and administer immediately.

Tablet: Swallow whole with a glass of water before morning meal; do not crush or chew.

Nasogastric/Gastric tube:

Oral suspension (using packets): Add 5 mL of water to a catheter tipped syringe and then add contents of a 2.5 mg packet (or 15 mL of water for the 10 mg packet). Immediately shake syringe and leave to thicken for 2 to 3 minutes; shake syringe again and within 30 minutes administer via NG or gastric tube (French size 6 or larger). Refill syringe with an equal amount of water, shake, and flush remaining contents through NG or gastric tube

Oral suspension (using capsules): The manufacturer of Prilosec does not give recommendations for extemporaneous preparation of omeprazole capsules for NG/OG administration. Consider using the packets for oral suspension. If packets are unavailable, methods of preparation of capsules for NG/OG administration have been described (Balaban 1997; Phillips 1996). An extemporaneously prepared suspension with extended stability may also be used (DiGiacinto 2000; Quercia 1997; Sharma 1999).

Storage

Capsules, tablets: Store at 15°C to 30°C (59°F to 86°F). Protect from light and moisture.

Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Bosutinib: Proton Pump Inhibitors may decrease the serum concentration of Bosutinib. Management: Consider alternatives to proton pump inhibitors, such as antacids or H2 receptor antagonists. Administer alternative agents more than 2 hours before or after bosutinib. Consider therapy modification

Darunavir: May decrease the serum concentration of Omeprazole. Monitor therapy

Dasatinib: Proton Pump Inhibitors may decrease the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of the proton pump inhibitor if some acid-reducing therapy is needed. Avoid combination

Delavirdine: Proton Pump Inhibitors may decrease the serum concentration of Delavirdine. Management: Chronic therapy with proton pump inhibitors (PPIs) should be avoided in patients treated with delavirdine. The clinical significance of short-term PPI therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Avoid combination

Dexmethylphenidate: Proton Pump Inhibitors may increase the absorption of Dexmethylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Dextroamphetamine: Proton Pump Inhibitors may increase the absorption of Dextroamphetamine. Specifically, the dextroamphetamine absorption rate from mixed amphetamine salt extended release (XR) capsules may be increased in the first hours after dosing. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Consider therapy modification

Escitalopram: Omeprazole may increase the serum concentration of Escitalopram. Management: Monitor for increased escitalopram toxicity with concomitant use of omeprazole. Recommendations for management of this interaction found in product labeling may differ by country. Consult appropriate labeling. Consider therapy modification

Fosphenytoin: Omeprazole may increase the serum concentration of Fosphenytoin. Fosphenytoin may decrease the serum concentration of Omeprazole. Monitor therapy

Gefitinib: Proton Pump Inhibitors may decrease the serum concentration of Gefitinib. Management: Avoid use of proton pump inhibitors (PPIs) with gefitinib when possible. If required, administer gefitinib 12 hours after administration of the PPI or 12 hours before the next dose of the PPI. Consider therapy modification

Ledipasvir: Proton Pump Inhibitors may decrease the serum concentration of Ledipasvir. Management: PPI doses equivalent to omeprazole 20 mg or lower may be given with ledipasvir under fasted conditions. Administration with higher doses of PPIs, 2 hours after a PPI, or in combination with food and PPIs may reduce ledipasvir bioavailability. Consider therapy modification

Methylphenidate: Proton Pump Inhibitors may increase the absorption of Methylphenidate. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Nilotinib: Proton Pump Inhibitors may decrease the serum concentration of Nilotinib. Management: Avoid this combination when possible since separation of doses is not likely to be an adequate method of minimizing the interaction. Consider therapy modification

Risedronate: Proton Pump Inhibitors may diminish the therapeutic effect of Risedronate. Proton Pump Inhibitors may increase the serum concentration of Risedronate. This applies specifically to use of delayed-release risedronate. Avoid combination

Secretin: Proton Pump Inhibitors may diminish the diagnostic effect of Secretin. Specifically, use of PPIs may cause a hyperresponse in gastrin secretion in response to secretin stimulation testing, falsely suggesting gastrinoma. Management: Avoid concomitant use of proton pump inhibitors (PPIs) and secretin, and discontinue PPIs several weeks prior to secretin administration, with the duration of separation determined by the specific PPI. See full monograph for details. Consider therapy modification

Test Interactions

Omeprazole may falsely elevate serum chromogranin A (CgA) levels. The increased CgA level may cause false-positive results in the diagnosis of a neuroendocrine tumor. Temporarily stop omeprazole ≥14 days prior to assessing CgA level; repeat level if initially elevated; use the same laboratory for all testing of CgA levels.

Warnings/Precautions

Concerns related to adverse effects:

• Carcinoma: In long-term (2-year) studies in rats, omeprazole produced a dose-related increase in gastric carcinoid tumors. While available endoscopic evaluations and histologic examinations of biopsy specimens from human stomachs have not detected a risk from short-term exposure to omeprazole, further human data on the effect of sustained hypochlorhydria and hypergastrinemia are needed to rule out the possibility of an increased risk for the development of tumors in humans receiving long-term therapy.

• Clostridium difficile-associated diarrhea (CDAD): Use of proton pump inhibitors (PPIs) may increase risk of CDAD, especially in hospitalized patients; consider CDAD diagnosis in patients with persistent diarrhea that does not improve. Use the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated.

• Cutaneous and systemic lupus erythematosus: Has been reported as new onset or exacerbation of existing autoimmune disease; most cases were cutaneous lupus erythematosus (CLE), most commonly, subacute CLE (occurring within weeks to years after continuous therapy). Systemic lupus erythematosus (SLE) is less common (typically occurs within days to years after initiating treatment) and occurred primarily in young adults up to the elderly. Discontinue therapy if signs or symptoms of CLE or SLE occur and refer to specialist for evaluation; most patients improve 4 to 12 weeks after discontinuation of omeprazole.

• Fractures: Increased incidence of osteoporosis-related bone fractures of the hip, spine, or wrist may occur with proton pump inhibitor (PPI) therapy. Patients on high-dose (multiple daily doses) or long-term (≥1 year) therapy should be monitored. Use the lowest effective dose for the shortest duration of time, use vitamin D and calcium supplementation, and follow appropriate guidelines to reduce risk of fractures in patients at risk.

• Hypomagnesemia: Reported rarely, usually with prolonged PPI use of ≥3 months (most cases >1 year of therapy). May be symptomatic or asymptomatic; severe cases may cause tetany, seizures, and cardiac arrhythmias. Consider obtaining serum magnesium concentrations prior to beginning long-term therapy, especially if taking concomitant digoxin, diuretics, or other drugs known to cause hypomagnesemia; and periodically thereafter. Hypomagnesemia may be corrected by magnesium supplementation, although discontinuation of omeprazole may be necessary; magnesium levels typically return to normal within 1 week of stopping.

• Interstitial nephritis: Acute interstitial nephritis has been observed in patients taking PPIs; may occur at any time during therapy and is generally due to an idiopathic hypersensitivity reaction. Discontinue if acute interstitial nephritis develops.

• Vitamin B12 deficiency: Prolonged treatment (>3 years) may lead to vitamin B12 malabsorption and subsequent vitamin B12 deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy (Lam, 2013).

Disease-related concerns:

• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.

• Gastrointestinal infection (eg, Salmonella, Campylobacter): Use of PPIs may increase risk of these infections.

• Clopidogrel: Proton pump inhibitors (PPIs) may diminish the therapeutic effect of clopidogrel, thought to be due to reduced formation of the active metabolite of clopidogrel. The manufacturer of clopidogrel recommends either avoidance of both omeprazole (even when scheduled 12 hours apart) and esomeprazole or use of a PPI with comparatively less effect on the active metabolite of clopidogrel (eg, pantoprazole). In contrast to these warnings, others have recommended the continued use of PPIs, regardless of the degree of inhibition, in patients with a history of GI bleeding or multiple risk factors for GI bleeding who are also receiving clopidogrel since no evidence has established clinically meaningful differences in outcome; however, a clinically significant interaction cannot be excluded in those who are poor metabolizers of clopidogrel (Abraham, 2010; Levine, 2011).

• Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (≤7 days) has been associated with a higher incidence of treatment failure. The American College of Gastroenterology recommends 10 to 14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey 2007).

• Self-medication (OTC use): When used for self-medication (OTC), notify health care provider before use if any of the following are present: heartburn for >3 months; frequent wheezing, particularly with heartburn; unexplained weight loss; nausea or vomiting; or stomach pain. Discontinue use and notify health care provider if heartburn continues or worsens; diarrhea occurs; if >14 days of therapy is needed; or if >1 course of therapy is needed every 4 months.

Monitoring Parameters

Pregnancy Considerations

An increased risk of hypospadias was reported following maternal use of proton pump inhibitors (PPIs) during pregnancy (Anderka 2012), but this was based on a small number of exposures and the same association was not found in another study (Erichsen 2012). Most available studies have not shown an increased risk of major birth defects following maternal use of omeprazole during pregnancy (Diav-Citrin 2005; Källén 2001; Lalkin 1998; Matok 2012; Pasternak 2010). When treating GERD in pregnancy, PPIs may be used when clinically indicated (ACT [Katz 2013]).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.